Reversal of pulmonary vascular remodeling in pulmonary hypertensive rats
Pulmonary hypertension is responsible for significant mortality and morbidity among newborns and infants. The pathology is characterized by pulmonary vascular remodeling with medial hypertrophy and adventitial thickening, leading to decreased gas exchange. Since it is unknown if these abnormalities are reversible, we analyzed these vascular changes in pulmonary hypertensive rats.Exposure of rats to hypobaric hypoxia for 4. weeks induced clinical signs of pulmonary hypertension, such as increased right ventricular systolic pressure, increased right ventricular weight and considerable pulmonary vascular remodeling. The vascular changes were associated with the expression of Non -Muscle Myosin Heavy Chain B in the pre-acinar vessels and an increased expression of alpha Smooth Muscle Actin, Smooth Muscle Myosin Heavy Chain 2 and Calponin in the intra-acinar vessels. The right ventricular systolic pressure and right ventricular weight gradually decreased after specific periods of recovery in normoxia, although this reversal did not reach baseline levels after six weeks at normoxia. However, the cellular changes in the pulmonary vasculature were completely reversed.Development of pulmonary hypertension is associated with an increase of synthetic perivascular cells in the pre-acinar arteries and an aberrant differentiation of perivascular cells in the smallest intra-acinar arteries. These cellular and structural changes in the pulmonary vasculature are completely reversible after recovery in normoxia.
|Keywords||Pulmonary hypertension, Rat model, Vascular remodeling|
|Persistent URL||dx.doi.org/10.1016/j.yexmp.2012.03.010, hdl.handle.net/1765/71369|
|Journal||Experimental and Molecular Pathology|
Sluiter, I, van Heijst, A.F.J, Haasdijk, R, van Kempen, M, de Munck, A, Reiss, I.K.M, … Rottier, R.J. (2012). Reversal of pulmonary vascular remodeling in pulmonary hypertensive rats. Experimental and Molecular Pathology, 93(1), 66–73. doi:10.1016/j.yexmp.2012.03.010